REGULATION OF GROWTH OF CULTURED SMOOTH-MUSCLE CELLS FROM DIABETIC RATS BY INTERLEUKIN-1-BETA - ROLE OF NITRIC-OXIDE

We examined the influence of streptozotocin-induced diabetes on the gr owth of cultured rat aortic smooth muscle cells in the presence of int erleukin-1 beta. Interleukin-1 beta induced a dose-dependent biphasic effect on proliferation of diabetic and control smooth muscle cells, c onsistent with the data on [H-3]thymidine incorporation and cell count s. However, the major effect of interleukin-1 beta was to stimulate gr owth of diabetic cells and inhibit growth of control cells. Furthermor e, interleukin-1 beta induced a dose-dependent increase in nitric oxid e (NO) release and in intracellular cyclic GMP accumulation: nitrite r elease was similar in both smooth muscle cell models but cyclic GMP ac cumulation was greater in diabetic cells than in controls. These resul ts suggest that the inhibitory loop involving NO is not effective enou gh to completely counterbalance the stimulatory effects of interleukin -1 beta on diabetic cells. Therefore, experimental diabetes may modify the interleukin-1 beta-regulated smooth muscle cell growth.